tbuckley/cabot-search huggingface dataset:
Incidence of skin cancer among patients with Waldenström macroglobulinemia: Analysis of the SEER database (2000-2019).
Authors: Alankrita Taneja, Rahul Mishra, Sumukh Arun Kumar, Jens Hillengass
Journal: Journal of Clinical Oncology (2023)

e18893 Background: The association between non-Hodgkin lymphoma, including chronic lymphocytic leukemia, and aggressive skin cancers is well established. We studied the incidence of melanoma and non-melanoma skin cancers (NM) skin malignancies (SM) among patients with Waldenstrom macroglobulinemia (WM). Methods: We used the SEER 17 registry to identify adult [Age &gt; 20] patients(pts) with an index diagnosis (dx) of WM between 2000- 2019. We included ICD-O-3 codes 9671/3 (Lymphoplasmacytic lymphoma) and 9761/ (Waldenstrom macroglobulinemia) to identify index dx. Only first of the two codes was used if both were mentioned for same pt. We excluded patients with diagnosis made from death certificate or autopsy. We used ICD-O-3/WHO 2008 codes assigned to melanoma of skin and other NM SM to identify subsequent diagnosis ( &gt; 2months after index diagnosis) of SM excluding basal cell and squamous cell cancers. SM were categorized using ICD-O-3 codes for histology. Follow up period was till December 2019. Data variables and standardized incidence ratio [SIR] for SM were obtained with multiple primary SIR analyses using SEER Stat v 8.4.0.1 software. Kaplan Meier method was used to estimate overall survival (OS) using R 4.2.2. Results: We identified 8099 patients with WM of which 68 patients (0.84%) had a subsequent dx of SM. WM and SM were diagnosed at median (IQR) ages of 69 (60-77) and 74 (67-81), with a median gap of 52 (30-95) months. Majority of WM survivors with SM were males (51 or 75%), white (100%) and older than 60 years of age (72%) at WM diagnosis. Almost half of the patients who developed SM underwent chemotherapy for WM (n = 35, 45%). The overall risk of developing SM was significantly higher in WM patients as compared to the general population [SIR (95%CI) = 1.34 (1.01-1.74) (p &lt; 0.05) for melanoma and 2.85 (1.52-4.87) (p &lt; 0.05) for NM]. Eleven different types of histology for SM were noted, with malignant melanoma, NOS (n = 30, 44%) and Merkel cell carcinoma (n = 7, 10%) being the most common melanoma and NM subtype (Table). The median survival after SM dx was 68 (55-NA) months. Conclusions: Patient with WM had higher risk of SM (melanoma and NM skin cancers, excluding basal cell and squamous cell cancers) compared to the general population. This study highlights the need for screening and counseling for skin cancers in WM patients in routine clinical practice. [Table: see text]
End-of-life spending analysis of randomized trial of machine learning nudges to prompt serious illness communication among patients with cancer.
Authors: Ravi Bharat Parikh, Jinbo Chen, Jonathan Heintz, Marc LaPergola, Warren Bilker, Mitesh S Patel, Justin E. Bekelman, Christopher Manz
Journal: Journal of Clinical Oncology (2023)

6515 Background: Early serious illness conversations (SICs) between oncology clinicians and patients in the outpatient setting may improve mood and quality-of-life among patients with cancer. However, the impact of early SIC “nudges” on end-of-life spending is unknown. Methods: This was a secondary analysis of a stepped-wedge randomized trial (NCT03984773) that randomized 9 medical oncology practices and their high-risk patients at a large academic institution to a behavioral intervention to increase SICs (performance reports and peer comparisons; precommitments for high-risk patients; weekly opt-out text prompts before high-risk encounters) vs. standard of care, between June 2019 and April 2020. We identified high-risk patients using a machine learning (ML) algorithm predicting 180-day mortality. This secondary analysis included 1187 (957 intervention, 230 control) patients with complete data who died by December 2020. We abstracted spending (defined as inflation-adjusted reimbursements for acute care [inpatient + ED], office/outpatient care, intravenous chemotherapy, other therapy [e.g. radiation], long-term care, and hospice) from the institution’s accounting system; we captured spending at University of Pennsylvania inpatient, outpatient, and pharmacy settings. To evaluate intervention impacts on spending, we used a two-part model: first, logistic regression to model zero versus nonzero spending, and second, generalized linear models with gamma distribution and log-link function to model daily mean spending in the last 180 days of life. Models were adjusted for clinic and wedge fixed effects and clustered at the oncologist level. Results: Median age at death was 68 years (IQR 15.5), 317 (27%) patients were non-White, and 448 (38%) patients had a SIC prior to death. The intervention was associated with lower mean spending in the last 180 days of life (mean daily spending $377.96 [intervention] vs. $449.92 [control]; adjusted mean difference -$75.33, 95% CI -$136.42, -$14.23 , p = 0.016) (Table), translating to $13,559 total adjusted savings. Intervention patients incurred lower mean daily spending for chemotherapy (adjusted difference -$51.35, p &lt; 0.001), office/outpatient care (-$14.59, p &lt; 0.001), and other therapy (-$10.35, p = 0.043). The intervention was not associated with differences in end-of-life spending for acute care utilization, long-term care, and hospice. Results were consistent for spending in the last 30 and 90 days of life and after adjusting for age, race, and ethnicity. Conclusions: A ML intervention to prompt SICs led to end-of-life savings, driven by decreased chemotherapy and outpatient spending. Clinical trial information: NCT03984773 . [Table: see text]
Strategies to increase accrual of underrepresented populations in Alliance NCTN trials.
Authors: Electra D. Paskett, Niveditha Subbiah, Marie Wood, Craig Steffens, Judith Salmon Kaur, Lucile L. Adams-Campbell, Suzanne George
Journal: Journal of Clinical Oncology (2023)

6509 Background: Accrual of underrepresented populations (URPs-racial and ethnic minorities, women, rural populations, and younger and older populations) to clinical trials has been historically low, hampering progress in cancer treatment, symptom intervention and prevention for all. In 2018, the Alliance for Clinical Trials in Oncology (Alliance), as a part of the NCI's National Clinical Trials Network (NCTN) and a Research Base for the NCI Community Oncology Research Program (NCORP) began a multi-pronged strategy to increase accrual of underrepresented minorities by race and ethnicity (URMs) to both treatment and cancer control trials conducted by the Alliance. Methods: Alliance leadership set a goal of 20% accrual for racial and ethnic minorities to all trials in 2018. The Health Disparities Committee (HDC) implemented several strategies over time including leadership promotion/expectation of goals; funding junior investigators and special projects focusing on URPs; working groups for specific populations in HDC; HDC co-chairs to selected protocols; translation services of patient facing materials; opening studies at NCORP Minority Underserved Sites; real time monitoring of accrual demographics, by Alliance and by site; protocols addressing aims for specific populations; closing protocol enrollment to majority populations; and increasing the study sample size to enroll additional minority participants to allow for analyzing intervention effects by subgroups. Results: Accrual data from 117 NCTN and NCORP trials led by Alliance was included from 2014-2022. Over time, accrual of racial and ethnic minorities increased from 13.6% to 25.3% for treatment and 13% to 21.5% for cancer control trials. This results in overall increase from 13.5 % to 23.6% of URMs for all trials, a 74.8% improvement. Conclusions: Intentional approaches to increase URMs has led to an increase in URM accruals to Alliance trials. Future strategies include implementation of the Alliance Patient Questionnaire to prospectively measure the prevalence of specific social determinants of health among patients enrolled to further expand the understanding and address the needs of unique population accrued to Alliance trials. In addition, accrual of women, rural populations, and younger and older adults (65+ years) are now being monitored over time to increase all URP accruals.
“It’s been a long journey:” A qualitative study of patient and caregiver experiences during multimodality treatment for locally advanced rectal cancer.
Authors: Kelsey S. Lau-Min, Riley Psenka, Katina Massad, Areej El-Jawahri, Jennifer S. Temel, Aparna Raj Parikh, Ryan David Nipp, Lara Traeger
Journal: Journal of Clinical Oncology (2023)

e24130 Background: Locally advanced rectal cancer (LARC) is treated with multimodality therapy including chemotherapy, radiation, and surgery to maximize the potential for cure. However, this aggressive treatment approach can result in substantial toxicity for patients, including life-altering changes in bowel, urinary, and sexual function as well as decrements in quality of life. We aimed to explore the lived experiences of patients and caregivers during multimodality treatment for LARC. Methods: We conducted a qualitative study of patients ≥18 years old undergoing multimodality treatment for LARC at the Massachusetts General Hospital, as well as their designated caregivers. We used purposive sampling to maximize variation in participant age, gender, and treatment status pre- versus post-surgery. Each participant completed a one-hour individual in-depth interview using a semi-structured interview guide covering treatment experiences, coping strategies, and supportive care needs. We audio recorded, transcribed, and coded interviews using an iterative approach, after which we analyzed the data using thematic analysis and constant comparison methods. Results: We included 21 patients (median age 51 years, 11 female, 18 white, 10 post-surgical resection) and 9 caregivers (median age 49 years, 8 white, 6 married/living with patient). Patients and caregivers reported that the lengthy and complex nature of treatment for LARC made it difficult for them to fully understand and navigate their treatment trajectories. The multimodality treatment approach presented several challenges with care coordination; discordant recommendations between treatment team members; and an overarching sense of unpredictability with respect to treatment timelines, complications, and impact on patients’ personal, work, and family lives. Patients and caregivers reported wishing that they had received more detailed information about each treatment phase upfront but recognized that the initial shock of a LARC diagnosis may have impeded their ability to absorb this new information. Many resorted to their own internet searches to address their unanswered questions but often found themselves returning to their treatment teams to clarify misperceptions and manage the additional distress they experienced online. Conclusions: Patients and caregivers face critical challenges in navigating treatment for LARC due to the lengthy, complex, and unpredictable nature of this treatment approach. Many resorted to their own internet searches and reported feeling misinformed, distressed, or regretful about the information found online. Findings from this study will inform the development of interventions to enhance information delivery and processing for patients undergoing multimodality treatment for LARC.
Estimating the impact of adjuvant atezolizumab in preventing recurrences and reducing costs in resectable early PD-L1 high non-small cell lung cancer in Europe.
Authors: Melina Arnold, Nick Jovanoski, Akanksha Tomar, Akansha Dubey, Yeun Mi Yim, Pavel Napalkov
Journal: Journal of Clinical Oncology (2023)

e20501 Background: Recurrences of non-small cell lung cancer (NSCLC) after surgery remain common and are associated with significant morbidity and mortality. Loco-regional or metastatic disease recurrence can lead to a substantial health care resource use and economic burden. The aim of this study was to estimate the effect of treating patients with early-stage NSCLC with adjuvant atezolizumab (ATZ) on the number of recurrences and direct healthcare costs in Germany, Spain, France Italy and the UK, together referred to as EU5. Methods: Using an epidemiological model, we estimated the reduction in loco-regional (LR) recurrences or distant metastases (DM) after adjuvant ATZ treatment following chemotherapy in operable NSCLC patients with PDL-1 expression of ≥ 50% on tumor cells (PD-L1 high), stage II-IIIA (AJCC 7 th edition staging), without EFGR or ALK alterations. We used data from cancer registries, published literature sources, and market research to obtain incidence rates, staging distribution, biomarker status data, and adjuvant treatment rates. Moreover, we used evidence on the disease-free survival (DFS) of patients on adjuvant ATZ from the IMpower010 (NCT02486718) clinical trial to calculate the projected reduction in the number of LR recurrences or DM over a 10-year period post-ATZ launch relative to best supportive care (BSC). The model considers the costs associated with treatment, management of adverse events, monitoring of the disease, and follow-up healthcare. Results: We project that between 2023 and 2033, 20,483 patients with resected PD-L1 high stage II-IIIA NSCLC would experience recurrence (LR, or DM, or both) in the EU5 if they were treated with BSC (adjuvant platinum-based chemotherapy) alone (Table 1). Assuming peak ATZ uptake of 75%, the model estimates that following adjuvant ATZ and chemotherapy, a total of 4,665 recurrences would be prevented in this patient population in the EU5 over 10 years, representing a 23% decrease in recurrence relative to BSC. These avoided recurrences in EU5 could translate into a considerable reduction in direct healthcare costs. Conclusions: Adjuvant ATZ following chemotherapy results in a considerable population-level reduction of loco-regional recurrence or distant metastasis in resected PD-L1 high stage II-IIIA NSCLC patients. This could translate into a substantial decrease in the economic and societal burden caused by the disease. [Table: see text]
Multi-modal and longitudinal characterization of the tumor and immune microenvironment from primary to in-transit and distant metastasis in acral melanoma.
Authors: Giuseppe Tarantino, Anne Zaremba, Tuulia Vallius, Florian Rambow, Roxanne Pelletier, Samira Makhzami, Lisa Zimmer, Antje Sucker, Elisabeth Livingstone, Eva Hadaschik, Christine Lian, George Murphy, Peter Sorger, David Liu, Dirk Schadendorf
Journal: Journal of Clinical Oncology (2023)

e21518 Background: Patients with in-transit metastases (ITM) in melanoma are a heterogeneous subset of patients where melanoma recurrence is anatomically detected between the site of the primary tumor and the draining lymph node. Notably, a significant subset of those patients has locoregional recurrences with long-term survival without progression to distant sites. The underlying mechanisms responsible for these distinct phenotypes are unknown. Methods: To understand the evolution from primary melanoma to in-transit and distant metastasis, we characterized the tumor and immune microenvironment among 9 patients with acral lentiginous melanoma using whole exome sequencing (WES), bulk RNAseq, snRNAseq and high-plex Cyclic Immunofluorescence (CyCIF) imaging. We further profiled the dynamics and the evolution of the tumor and immune compartments using 28 tumor samples obtained longitudinally over 9 years from a single patient (pt222) with recurrent in-transit and distant metastases undergoing CDK4/6, MEK inhibition and immune checkpoint blockade. Results: Our cohort included 5 patients that progressed from ITM to distant disease and 4 patients with only local recurrence and without distant progression (Table). WES profiling identified enriched RAS mutations (5 out of 9), independent of progression and treatment response. Pt222 showed multiple morphological features related to aggressive tumor growth and high risk of recurrence such as clefting, ulceration detected within the primary tumor by the histopathological assessment of the H&amp;E section. Phylogenetic analysis revealed co-evolution of 7 genetic lineages that shared 35 clonal mutations, including NRAS p.Q61H, with independent resistance-associated alterations. The metastases at distant sites emerged from a lineage featured with high aneuploidy and tumor mutational burden (TMB). The brain metastasis showed the highest TMB and aneuploidy. Bulk RNAseq deconvolution, snRNAseq, CyCIF and H&amp;E revealed low and heterogeneous immune composition among different samples and lineages with macrophages and DCs as dominant populations. Interestingly, we did not observe the lineage characterized by the highest absolute immune infiltrates after ICB treatment. Another specific lineage that disappeared after the treatment with ICB showed angiotropic growth and the over-expression of a WNT-betacatenin transcriptional signature linked with T cell exclusion. An orthogonal validation using bulk RNAseq, snRNAseq and CyCIF confirmed these findings. Conclusions: This study helps define a high-resolution map of the evolutionary dynamics from primary to in-transit and distant metastasis. [Table: see text]
Overall and non-lung cancer incidence in the national lung screening trial (NLST) as indicators of potential for multi-cancer screening.
Authors: Ellen T. Chang, Sam M. Janes, Allan Hackshaw, Christina A. Clarke Dur, Diana SM Buist, Earl A. Hubbell
Journal: Journal of Clinical Oncology (2023)

10633 Background: Single-cancer screening strategies address only one component of the overall population cancer burden. Even high-risk populations in single-cancer screening trials experience a considerable burden of other cancer incidence; therefore, we assessed non-lung cancer incidence in the NLST to evaluate the proportion of unscreened cancers. Methods: The NLST was a randomized controlled trial of screening for lung cancer in adults aged 55–74 years with ≥30 pack-years of smoking history, enrolled in 2002–2004 and actively followed through 2009. Incident cancers were identified via participant questionnaires, death certificates, and direct notifications, and confirmed by medical record abstraction. The present analysis includes first invasive primary cancers diagnosed after study randomization. Non-lung cancer incidence was similar between the two trial arms, which were therefore combined for analysis. Results: Among 53 229 subjects (median follow-up 6.5 years), the incidence of any first primary cancer was 1941 per 100 000 person-years, of which 1327 per 100 000 (68%) was non-lung cancer. Non-lung cancer incidence rates exceeded that for lung cancer in all 5-year age categories (especially at younger ages) and all quintiles of smoking pack-years (especially with fewer pack-years). After lung cancer, the most common cancers were other leading cancer types in the general US population, as well as other smoking-related cancers (Table). No recommended population-based screens exist for 54% of observed cancer cases (3332 of 6142, excluding lung, colon/rectum, female breast, and cervix). Conclusions: In the NLST, only 32% of first primary cancer incidence was lung; non-lung cancer comprised 68%, and most cases were cancer types with no generally recommended screening strategy. Even in a high-risk population, a single-cancer screening test misses most cancers, illustrating the value of multi-cancer screening tests that can detect a broad spectrum of cancers and, therefore, have the potential to address a currently inaccessible portion of cancer morbidity and mortality. [Table: see text]
Disparities in germline genetic testing results from a cohort of 493,515 black and white patients.
Authors: Rachel Wyatt, Sarah M. Nielsen, Elaine Chen, Brandie Heald, Edward D. Esplin, Gail Elizabeth Tomlinson
Journal: Journal of Clinical Oncology (2023)

10550 Background: When undergoing germline genetic testing (GGT), Black patients (pts) are more likely than non-Hispanic White (NHW) pts to receive uncertain results and less likely to receive definitive molecular diagnoses as the Black genome is less well-characterized. As GGT is increasingly pertinent to cancer care, it is important to explore the scope of these disparities. Methods: A retrospective cohort of clinician-reported Black and NHW pts who underwent GGT (43-84 genes) from 2015-2022 was evaluated. Frequencies of pathogenic/likely pathogenic (P/LP) and variant of uncertain significance (VUS) results were compared between Black and NHW pts. Rate and type of VUS reclassifications were also compared. Differences in proportions were determined using Chi-square test and significance was set at 0.05. Results: The cohort consisted of 493,515 pts (48,684 [10%] Black and 444,831 [90%] NHW). VUS results were significantly more frequent and P/LP results significantly less frequent for Black compared to NHW pts (46% vs. 32% and 9 vs.13%, respectively). This was also true for pts who reported a history of cancer, across all common hereditary cancer types (Table). Comparing Black to NHW pts, there were more unique instances of VUS reclassifications over time (13% of 13,629 vs. 9% of 53,195 unique VUS), including 12% vs. 8% downgraded to benign/likely benign and 0.9% vs. 1.3% upgraded to P/LP. Conclusions: Lower rates of actionable results limit risk-reducing interventions for Black pts and their families. However, VUS rates continue to decline, particularly in Black pts, as more individuals (of any race or ethnicity) are sequenced. Clinicians can be reassured that most (but not all) VUS that are reclassified are downgraded to benign. [Table: see text]
Racioethnic differences in missing data in the national cancer database: A window into inequities in cancer care.
Authors: Vignesh Raman, John Migaly, Rachel Adams Greenup, Betty Caroline Tong, Oluwadamilola Motunrayo Fayanju
Journal: Journal of Clinical Oncology (2023)

e18502 Background: While the National Cancer Database (NCDB) is frequently used for observational studies about cancer care including disparities, study populations are often overwhelmingly White. The aim of this study was to assess racioethnic inequities in the NCDB by characterizing the completeness of data in the registry. We hypothesized that Black and Hispanic patients are more likely, compared to White patients, to have missing data about staging, treatment, and survival. Methods: We used the 2004-2016 NCDB files for breast, colon, and lung cancer focusing on non-Hispanic White, Black, and Hispanic patients. The primary outcome was the comparative missingness in data between the three racioethnic groups, measured using multivariable logistic regression models. A stepwise study progression from diagnosis of cancer, histology, clinical staging, treatment documentation, survival, and guideline-concordant care was used. Results: Compared to the U.S. Census data from 2010, Black and especially Hispanic patients were much less likely to be registered in the NCDB compared to Whites. Black and Hispanic patients were also more likely to have missing or non-usable histology data, incomplete or missing clinical staging, and treatment documentation (Table). Survival and follow-up documentation was similar between the three groups. Black and Hispanic patients were less likely to receive surgery for stage I-III disease compared to White patients. Conclusions: Our study suggests that the NCDB may be a limited resource for study of cancer in Black and Hispanic patients, and that inequities in missing data in its own structure may reflect racioethnic inequities in cancer care in the United States. Summary of fraction of missing treatment status, by malignancy, stratified by race/ethnicity in the NCDB. Data are represented as count (percent) unless otherwise noted. The p values are obtained by the Pearson’s chi squared test. Results from a multivariable logistic regression examining the odds of missing treatment status are provided for each malignancy as well. [Table: see text]